Lefer A M, Smith E F, Araki H, Smith J B, Aharony D, Claremon D A, Magolda R L, Nicolaou K C
Proc Natl Acad Sci U S A. 1980 Mar;77(3):1706-10. doi: 10.1073/pnas.77.3.1706.
Carbocyclic thromboxane A2 [2 beta (Z),3 alpha- (1E,3R*)-3-(3-hydroxy(1-octenyl)-bicyclo[3.1.1]hept-2-yl-5-heptenoic acid], a stable analog of thromboxane A2, has been tested for its physiologic properties. Carbocyclic thromboxane A2 is a potent coronary vasoconstrictor, stimulating cornonary vascular smooth muscle at concentrations as low as 29 pM. At 1-5 micro M it is also an inhibitor of arachidonic-acid- and endoperoxide-induced aggregation of platelets. At 200 nM it stimulated the release of lysosomal hydrolases from large granule fractions of liver homogenate. It inhibited thromboxane synthesis in platelets, although it did not inhibit synthesis of prostacyclin in ram seminal vesicles. Thus, carbocyclic thromboxane A2, a molecule closely related to thromboxane A2, separates coronary vasoconstrictor from platelet-aggregating activity. The constrictor activity predominates in vivo; carbocyclic thromboxane A2 induces coronary vasoconstriction leading to myocardial ischemia and sudden death in rabbits in the absence of pulmonary or coronary thrombosis.
碳环血栓素A2 [2β(Z),3α-(1E,3R*)-3-(3-羟基(1-辛烯基)-双环[3.1.1]庚-2-基)-5-庚烯酸]，一种血栓素A2的稳定类似物，已对其生理特性进行了测试。碳环血栓素A2是一种强效的冠状动脉血管收缩剂，在低至29 pM的浓度下就能刺激冠状动脉血管平滑肌。在1 - 5微摩尔时，它也是花生四烯酸和内过氧化物诱导的血小板聚集的抑制剂。在200 nM时，它刺激肝匀浆大颗粒部分溶酶体水解酶的释放。它抑制血小板中血栓素的合成，尽管它不抑制公羊精囊中环前列腺素的合成。因此，与血栓素A2密切相关的分子碳环血栓素A2，将冠状动脉血管收缩活性与血小板聚集活性区分开来。收缩活性在体内占主导；在没有肺或冠状动脉血栓形成的情况下，碳环血栓素A2可诱导家兔冠状动脉血管收缩，导致心肌缺血和猝死。
